It is known that certain compounds produce an organophosphate-induced toxicity both in humans and other mammals. It is known that certain compounds will diminish the level of acetylcholine in nerve terminals by the inhibition of the sodium-dependent high affinity choline uptake mechanism. These compounds such as hemicholinium-3 present a complex spectrum of pharmacological effects, including blockade of neuromuscular transmission. It was, therefore, initially believed that compounds such as hemicholinium may prove useful as nerve terminal blockers for organophosphorous toxicity.
Organophosphorous toxicity produces uncontrolled impulses which move up and down the neurotransmitters and ultimately can cause death. This forms the basis for nerve gas or war gases, such as tabun and sarin, soman. It goes without saying that there is a continuing need for the development of successful antagonists which when administered will render nerve gas harmless.
Another much more common risk that occurs in day-to-day life is the exposure of agricultural employees to highly toxic insecticides and herbicides. Many of these are organophosphorous compounds and will stimulate, although to a lesser degree than war gas, the same symptoms of organophosphate toxicity. Typical examples of such agricultural insecticides would be the trademarked brands Peraoxon and Parathion.
It is not at all uncommon for farm workers to be exposed to heavy doses of insecticides/herbicides during spring application to cultivated fields. When this occurs, especially if caution is not taken, there is a very real risk of being overcome. This can occur from either inhalation of vapors of the organophosphate insecticide/herbicides, or it can come from absorption directly through the skin, since many of these compounds can be readily absorbed.
It can therefore be seen that there is a real and continuing need to develop antagonists for these agricultural chemicals known to induce organophosphate toxicity. Such antagonists could be administered in a prophylactic way before exposure to the chemicals, or alternatively in a therapeutic treatment way after exposure to the chemicals.
Accordingly, it is a primary objective of the present invention to provide new compounds which have the capability of neutralizing many of the components of organophosphate induced toxicity.
Another objective of the present invention is to provide compounds which can be used as effective blockers for neutralizing components against war gases, such as nerve gas.
Another objective of the present invention is to provide certain compounds which can be used to neutralize or block organophosphate induced toxicity caused by certain insecticides/herbicides.
Another objective of the present invention is to provide compounds which not only have the capability of neutralizing many of the components of organophosphate induced toxicity but which have very high therapeutic indexes, indicating safety in use.
The method and manner of accomplishing each of these objectives, as well as others, will be apparent from the detailed description of the invention which follows hereinafter.